Evaluation of superporous hydrogel (SPH) and SPH composite in porcine intestine ex-vivo: assessment of drug transport, morphology effect, and mechanical fixation to intestinal wall

被引:39
作者
Dorkoosh, FA [1 ]
Borchard, G [1 ]
Rafiee-Tehrani, M [1 ]
Verhoef, JC [1 ]
Junginger, HE [1 ]
机构
[1] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Dept Pharmaceut Technol, NL-2300 RA Leiden, Netherlands
关键词
superporous hydrogels; superporous hydrogel composite; intestinal drug transports; peptide drug; mechanical fixation; morphology of porcine intestine;
D O I
10.1016/S0939-6411(01)00222-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of this study was to investigate the potential of superporous hydrogel (SPH) and SPH composite (SPHC) polymers to enhance the transport of N-alpha-benzoyl-arginine ethylester (BAEE) and fluorescein isothiocyanate-dextran 4400 (FD4) across porcine intestinal epithelium ex-vivo, and to study any possible morphological damage to the epithelium by applying these polymers. In addition, the ability of these polymers to attach to the gut wall by mechanical pressure was examined by using a specifically designed centrifuge model. The transport of BAEE and FD4 across the intestinal mucosa was enhanced 2- to 3-fold by applying SPHC polymer in comparison to negative control. No significant morphological damage was observed by applying these polymers inside the intestinal lumen. Moreover, the SPH and SPHC polymers were able to attach mechanically to the intestinal wall by swelling and did not move in the intestinal lumen even when a horizontal force of 13 gms(-2) was applied. In conclusion, these polymers are appropriate vehicles for enhancing the intestinal absorption of peptide and protein drugs. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:161 / 166
页数:6
相关论文
共 27 条
  • [1] Enhancement of the intestinal absorption of peptides and nonpeptides
    Aungst, BJ
    Saitoh, H
    Burcham, DL
    Huang, SM
    Mousa, SA
    Hussain, MA
    [J]. JOURNAL OF CONTROLLED RELEASE, 1996, 41 (1-2) : 19 - 31
  • [2] SITE DEPENDENCE OF ABSORPTION-PROMOTING ACTIONS OF LAURETH-9, NA SALICYLATE, NA2EDTA, AND APROTININ ON RECTAL, NASAL, AND BUCCAL INSULIN DELIVERY
    AUNGST, BJ
    ROGERS, NJ
    [J]. PHARMACEUTICAL RESEARCH, 1988, 5 (05) : 305 - 308
  • [3] The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins
    Bernkop-Schnurch, A
    [J]. JOURNAL OF CONTROLLED RELEASE, 1998, 52 (1-2) : 1 - 16
  • [4] Regulation of the intestinal epithelial paracellular barrier
    Daugherty, AL
    Mrsny, RJ
    [J]. PHARMACEUTICAL SCIENCE & TECHNOLOGY TODAY, 1999, 2 (07): : 281 - 287
  • [5] TRANSIT OF PHARMACEUTICAL DOSAGE FORMS THROUGH THE SMALL-INTESTINE
    DAVIS, SS
    HARDY, JG
    FARA, JW
    [J]. GUT, 1986, 27 (08) : 886 - 892
  • [6] Preparation and NMR characterization of superporous hydrogels (SPH) and SPH composites
    Dorkoosh, FA
    Brussee, J
    Verhoef, JC
    Borchard, G
    Rafiee-Tehrani, M
    Junginger, HE
    [J]. POLYMER, 2000, 41 (23) : 8213 - 8220
  • [7] Development and characterization of a novel peroral peptide drug delivery system
    Dorkoosh, FA
    Verhoef, JC
    Borchard, G
    Rafiee-Tehrani, M
    Junginger, HE
    [J]. JOURNAL OF CONTROLLED RELEASE, 2001, 71 (03) : 307 - 318
  • [8] ACYLCARNITINES - DRUG ABSORPTION-ENHANCING AGENTS IN THE GASTROINTESTINAL-TRACT
    FIX, JA
    ENGLE, K
    PORTER, PA
    LEPPERT, PS
    SELK, SJ
    GARDNER, CR
    ALEXANDER, J
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 251 (03): : G332 - G340
  • [9] INTESTINAL MUCINS IN HEALTH AND DISEASE
    FORSTNER, JF
    [J]. DIGESTION, 1978, 17 (03) : 234 - 263
  • [10] FORTH W, 1975, INT ENCY PHARM THERA, V1, P1